A5039802892- Parkinson's Disease Mechanisms and Treatments
- Neurological disorders and treatments
- Zebrafish Biomedical Research Applications
- Fish biology, ecology, and behavior
- Retinal Development and Disorders
- Lysosomal Storage Disorders Research
- Autophagy in Disease and Therapy
- Advanced Neuroimaging Techniques and Applications
- Hallucinations in medical conditions
- Cellular transport and secretion
- Neuroscience and Neuropharmacology Research
- Botulinum Toxin and Related Neurological Disorders
- Nuclear Receptors and Signaling
- CRISPR and Genetic Engineering
- Mitochondrial Function and Pathology
- Photoreceptor and optogenetics research
- Neurogenesis and neuroplasticity mechanisms
- RNA regulation and disease
- Neurobiology and Insect Physiology Research
- Neuroinflammation and Neurodegeneration Mechanisms
- interferon and immune responses
- Plant Physiology and Cultivation Studies
- Genetic Neurodegenerative Diseases
- Fish Biology and Ecology Studies
- Spatial Neglect and Hemispheric Dysfunction
Niigata University
2017-2025
Technische Universität Braunschweig
2012-2023
Creative Commons
2022
University of Miyazaki
2014-2019
Mie University
2003-2019
Kyoto University
2009-2015
Zoological Institute
2014
Laboratoire d’immunologie intégrative du cancer
2014
Faculty (United Kingdom)
2014
Japan Science and Technology Agency
2009-2013
Significance We have resolved an efferent connection map of the zebrafish cerebellar Purkinje cells (PCs), showing that PC efferents represent one highest conserved circuitries throughout vertebrates. Moreover, by physiological characterization and functional interrogation using optogenetics in freely moving zebrafish, we identified distinct regions responsible for controlling specific but different stereotypic behaviors. This finding indicates output layer is topographically organized shows...
Abstract Mitochondrial dysfunction and lysosomal have been implicated in Parkinson’s disease (PD), but the links between these dysfunctions PD pathogenesis are still largely unknown. Here we report that cytosolic dsDNA of mitochondrial origin escaping from degradation was shown to induce cytotoxicity cultured cells phenotypes vivo. The depletion PINK1, GBA and/or ATP13A2 causes increases induces type I interferon (IFN) responses cell death lines. These rescued by overexpression DNase II, a...
Dementia occurs frequently in patients with Parkinson's disease (PD). However, the nature of dementing process remains controversial. We evaluated various cognitive functions PD, compared fractional anisotropy (FA) values between PD and without dementia.Thirty-seven consecutive Hoehn-Yahr stage III or IV participated this study. Patients were divided into two groups: (i) dementia group (PDD) (ii) (PDND). There 11 PDD 26 PDND cases. Ten controls also studied.The showed significant FA...
Objective Loss of function mutations in PINK1 typically lead to early onset Parkinson disease (PD). Zebrafish ( Danio rerio ) are emerging as a powerful new vertebrate model study neurodegenerative diseases. We used pink1 mutant pink −/− zebrafish line with premature stop mutation (Y431*) the kinase domain identify molecular mechanisms leading mitochondrial dysfunction and loss dopaminergic neurons deficiency. Methods The effect deficiency on number neurons, function, morphology was assessed...
Homozygous mutations in the glucocerebrosidase (GBA) gene result Gaucher disease (GD), most common lysosomal storage disease. Recent genetic studies have revealed that GBA confer a strong risk for sporadic Parkinson's (PD). To investigate how cause PD, we generated nonsense mutant (GBA-/-) medaka are completely deficient (GCase) activity. In contrast to perinatal death humans and mice lacking GCase activity, GBA-/- survived months, enabling analysis of pathological progression. displayed...
Parkinson's disease (PD) is a neurodegenerative characterized by α-synuclein-positive inclusion bodies and loss of neurons, including dopaminergic neurons. Difficulty in replicating PD phenotypes using animal models partly limits the understanding therapy required. Although strongly associated with aging, most experimental animals may not exhibit age-related symptoms. Herein, we demonstrate that Nothobranchius furzeri, rapidly aging teleost short life span, exhibits age-dependent...
Pathophysiology of hallucinations in Parkinson's disease is poorly understood. This study investigated relationships between visual and acuity. Twenty-six consecutive patients with participated this study. Patients were divided into two groups: (VH group) those without (no-VH group). Unaided corrected eyesight was evaluated all patients, if frequent use prescription glasses or contact lenses involved, using these also measured as the patient's own best eyesight. If a patient did not lenses,...
Here, we report that normal ATP13A2 localizes in the lysosome, whereas disease‐associated variants remain endoplasmic reticulum. Cathepsin D activity was decreased ATP13A2‐knockdown cells displayed lysosome‐like bodies characterized by fingerprint‐like structures. Furthermore, an atp13a2 mutation medaka fish resulted dopaminergic neuronal death, cathepsin activity, and structures brain. Based on these results, lysosome abnormality is very likely to be primary cause of KRS/PARK9.
α-Synuclein accumulates in Lewy bodies, and this accumulation is a pathological hallmark of Parkinson's disease (PD). Previous studies have indicated causal role α-synuclein the pathogenesis PD. However, molecular cellular mechanisms toxicity remain elusive. Here, we describe novel phosphorylation site at T64 detailed characteristics post-translational modification. was enhanced both PD models human brains. T64D phosphomimetic mutation led to distinct oligomer formation, structure similar...
Abstract Little is known about the developing mechanisms of visual hallucinations in Parkinson's disease. This study aimed to investigate perfusion changes parkinsonian patients with using n ‐isopropyl‐ p ‐[ 123 I]iodoamphetamine ([ I]IMP) single photon emission computed tomography imaging. A total 70 consecutive patients, including 31 hallucinations, and 39 without participated this study. Patients severe cognitive impairment (Mini‐Mental State Examination score < 20), nonvisual or...
Parkinson's disease (PD) is a common neurodegenerative disorder characterized by selective dopaminergic cell loss in the substantia nigra, but its pathogenesis remains unclear. The recessively inherited familial PD genes PARK2 and PARK6 have been attributed to mutations Parkin PTEN-induced kinase 1 (PINK1) genes, respectively. Recent reports suggest that PINK1 works upstream of same pathway regulate mitochondrial dynamics and/or conduct autophagic clearance damaged mitochondria. This...
Gait disturbance is a cardinal symptom in patients with Parkinson's disease. Among the gait disturbances, freezing of unique and troublesome symptom, but its mechanism unclear. We compared brain perfusion images using three-dimensional stereotactic surface projection analysis N-isopropyl-p-123I iodoamphetamine single photon emission computed tomography between disease those without. Twenty-four cases (freezing group) gait, 31 Hoehn Yahr stage-matched (no without were studied. Bilateral...
Recent findings suggest that a defect in the ubiquitin-proteasome system plays an important role pathogenesis of Parkinson's disease (PD). A previous report (McNaught et al. 2004) demonstrated rats systemically injected with proteasome inhibitors exhibited PD-like clinical symptoms and pathology. However, because these have not been consistently replicated, this model is commonly used to study PD. We medaka fish test effect systemic administration high level accessibility cerebrospinal fluid...
The objective was to compare brain perfusion image using 3-dimensional stereotactic surface projection analysis of N-isopropyl-p-123I iodoamphetamine single photon emission computed tomography between Parkinson's disease patients with a high frontal assessment battery score and those low score. Thirty nondemented were studied. Patients divided into 2 groups: high-scoring group whose 12 or more low-scoring 11 less. included 21 patients, the 9 patients. They underwent tomography, we analyzed...
It is generally assumed that executive dysfunctions in Parkinson's disease (PD) are caused by degeneration of the basal ganglia or frontal cortex both. However, there have been few studies investigating relationship between and cerebral pathological change. The objective this study was to evaluate various cognitive functions non-demented patients with PD, compare fractional anisotropy (FA) values PD without dysfunction.Twenty-one consecutive were enrolled study. Patients divided into two...
In recent years, considerable effort has been devoted to the development of a fish model for Parkinson's disease (PD) examine pathological mechanisms neurodegeneration. To effectively evaluate PD pathology, ability accurately and reliably count dopaminergic neurons is important. However, there currently no such standardized method. Due relatively small number in fish, stereological estimation would not be suitable. addition, serial sectioning requires proficiency lose any sections, it...
Abstract The African turquoise killifish Nothobranchius furzeri ( N. ) is a useful model organism for studying aging, age-related diseases, and embryonic diapause. CRISPR/Cas9-mediated gene knockout Tol2 transposon-mediated transgenesis in have been reported previously. However, these methods take time to generate transgenic fish. In addition, knock-in technology that inserts large DNA fragments as fluorescent reporter constructs into the target has not yet established. Here, we show...